tbuckley/cabot-search huggingface dataset:
Effect of a Gun Safety Video on Children’s Behavior Around Real Guns
Authors: Sophie L. Kjærvik, Brad J. Bushman
Journal: JAMA Pediatrics (2023)

Importance Firearms are the leading cause of death for children in the US. It is therefore crucial to identify effective ways to reduce firearm injuries among children. Objective To test the effectiveness of a gun safety video vs a car safety video on decreasing unsafe behaviors around real guns after exposure to a violent movie with vs without guns. Design, Setting, and Participants Of 245 participants aged 8 to 12 years, 226 were tested (13 did not complete the laboratory portion, 4 had technical problems, and 2 did not respond to follow-up inquiries). Data were collected from February 2 to October 16, 2022. Participants were recruited via Facebook ads, ResearchMatch, and parent or guardian referrals. The study was conducted in 2 parts. Children watched a safety video at home 1 week before coming to the laboratory at The Ohio State University. Interventions Pairs of children were randomly assigned to watch a 1-minute gun or car safety video at home. In the laboratory, they were randomly assigned to watch a 20-minute clip from a violent PG-rated movie with or without guns. Next, they played with games and toys for 20 minutes in another room that contained 2 disabled 9-mm handguns hidden in a file cabinet drawer. Sessions were videotaped via a hidden camera. Main Outcomes and Measures Outcomes were whether children told an adult, touched a handgun, handled it, or pulled the trigger. Control variables were age, gender, race and ethnicity, trait aggressiveness, age-inappropriate media exposure, firearm attitude and interest, presence of firearms at home, and whether children had taken a firearm safety course. Results Of 226 children (mean [SD] age, 9.99 [1.38] years; 113 [52.3%] male), 216 (95.6%) found a gun and were included in analyses. Those who saw the gun (vs car) safety video were more likely to tell an adult about the gun they found (38 of 112 [33.9%] vs 11 of 104 [10.6%]), were less likely to touch the gun (44 of 112 [39.3%] vs 70 of 104 [67.3%]), held the gun fewer seconds if they did touch it (mean [SD], 42.04 [121.46] vs 98.96 [195.10]), were less likely to pull the trigger at all (10 of 112 [8.9%] vs 31 of 104 [29.8%]), and pulled the trigger fewer times (mean [SD], 4.20 [20.17] vs 7.23 [15.75]). Being male, exposure to age-inappropriate movies, and gun interest were related to unsafe behavior. Prior completion of a firearm safety course, having guns at home, and negative gun attitudes were related to safe behavior. Conclusions In this trial of children assigned to watch a gun or car safety video, watching a gun safety video reduced children’s unsafe behavior around real guns. Children who had previously taken a gun safety course, had guns in the home, and had negative attitudes toward guns were less likely to engage in unsafe behavior around real guns. To encourage safe firearm behavior, children should be educated about gun safety and should not watch age-inappropriate media. Trial Registration ClinicalTrials.gov Identifier: NCT05257837
Opioid Dosing by Primary Care Professionals—A Call for Humility
Authors: Mitchell H. Katz, Deborah Grady
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Author Correction: High- or low-dose preoperative ipilimumab plus nivolumab in stage III urothelial cancer: the phase 1B NABUCCO trial
Authors: Jeroen van Dorp, Christodoulos Pipinikas, Britt B. M. Suelmann, Niven Mehra, Nick van Dijk, Giovanni Marsico, Maurits L. van Montfoort, Sophie Hackinger, Linde M. Braaf, Tauanne Amarante, Charlaine van Steenis, Kirsten McLay, Antonios Daletzakis, Daan van den Broek, Maaike W. van de Kamp, Kees Hendricksen, Jeantine M. de Feijter, Thierry N. Boellaard, Richard P. Meijer, Antoine G. van der Heijden, Nitzan Rosenfeld, Bas W. G. van Rhijn, Greg Jones, Michiel S. van der Heijden
Journal: Nature Medicine (2023)
Trial of Solanezumab in Preclinical Alzheimer’s Disease
Authors: Reisa A. Sperling, Michael C. Donohue, Rema Raman, Michael S. Rafii, Keith Johnson, Colin L. Masters, Christopher H. van Dyck, Takeshi Iwatsubo, Gad A. Marshall, Roy Yaari, Michele Mancini, Karen C. Holdridge, Michael Case, John R. Sims, Paul S. Aisen
Journal: New England Journal of Medicine (2023)

Trials of monoclonal antibodies that target various forms of amyloid at different stages of Alzheimer's disease have had mixed results. Download a PDF of the Research Summary. We tested solanezumab, which targets monomeric amyloid, in a phase 3 trial involving persons with preclinical Alzheimer's disease. Persons 65 to 85 years of age with a global Clinical Dementia Rating score of 0 (range, 0 to 3, with 0 indicating no cognitive impairment and 3 severe dementia), a score on the Mini–Mental State Examination of 25 or more (range, 0 to 30, with lower scores indicating poorer cognition), and elevated brain amyloid levels on 18F-florbetapir positron-emission tomography (PET) were enrolled. Participants were randomly assigned in a 1:1 ratio to receive solanezumab at a dose of up to 1600 mg intravenously every 4 weeks or placebo. The primary end point was the change in the Preclinical Alzheimer Cognitive Composite (PACC) score (calculated as the sum of four z scores, with higher scores indicating better cognitive performance) over a period of 240 weeks. A total of 1169 persons underwent randomization: 578 were assigned to the solanezumab group and 591 to the placebo group. The mean age of the participants was 72 years, approximately 60% were women, and 75% had a family history of dementia. At 240 weeks, the mean change in PACC score was −1.43 in the solanezumab group and −1.13 in the placebo group (difference, −0.30; 95% confidence interval, −0.82 to 0.22; P=0.26). Amyloid levels on brain PET increased by a mean of 11.6 centiloids in the solanezumab group and 19.3 centiloids in the placebo group. Amyloid-related imaging abnormalities (ARIA) with edema occurred in less than 1% of the participants in each group. ARIA with microhemorrhage or hemosiderosis occurred in 29.2% of the participants in the solanezumab group and 32.8% of those in the placebo group. Solanezumab, which targets monomeric amyloid in persons with elevated brain amyloid levels, did not slow cognitive decline as compared with placebo over a period of 240 weeks in persons with preclinical Alzheimer's disease. (Funded by the National Institute on Aging and others; A4 ClinicalTrials.gov number, NCT02008357.) QUICK TAKE VIDEO SUMMARYSolanezumab in Preclinical Alzheimer's Disease 02:05
Ancestry-driven metabolite variation provides insights into disease states in admixed populations
Authors: Kaylia M. Reynolds, Andrea R. V. R. Horimoto, Bridget M. Lin, Ying Zhang, Nuzulul Kurniansyah, Bing Yu, Eric Boerwinkle, Qibin Qi, Robert Kaplan, Martha Daviglus, Lifang Hou, Laura Y. Zhou, Jianwen Cai, Saame Raza Shaikh, Tamar Sofer, Sharon R. Browning, Nora Franceschini
Journal: Genome Medicine (2023)

Abstract Background Metabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk. Methods We performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data. Results By leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC , respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1 , is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent. Conclusions Our findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations.
MSV: a modular structural variant caller that reveals nested and complex rearrangements by unifying breakends inferred directly from reads
Authors: Markus Schmidt, Arne Kutzner
Journal: Genome biology (2023)

Structural variant (SV) calling belongs to the standard tools of modern bioinformatics for identifying and describing alterations in genomes. Initially, this work presents several complex genomic rearrangements that reveal conceptual ambiguities inherent to the representation via basic SV. We contextualize these ambiguities theoretically as well as practically and propose a graph-based approach for resolving them. For various yeast genomes, we practically compute adjacency matrices of our graph model and demonstrate that they provide highly accurate descriptions of one genome in terms of another. An open-source prototype implementation of our approach is available under the MIT license at https://github.com/ITBE-Lab/MA .
Optical Genome Mapping Identifies Novel Recurrent Structural Alterations in Childhood ETV6::RUNX1+ and High Hyperdiploid Acute Lymphoblastic Leukemia
Authors: Danielle Brandes, Layal Yasin, Karin Nebral, Jana Ebler, Dagmar Schinnerl, Daniel Picard, Anke K. Bergmann, Jubayer Alam, Stefan Köhrer, Oskar A. Haas, Andishe Attarbaschi, Tobias Marschall, Martin Stanulla, Arndt Borkhardt, Triantafyllia Brozou, Ute Fischer, Rabea Wagener
Journal: HemaSphere (2023)

The mutational landscape of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the most common pediatric cancer, is not fully described partially because commonly applied short-read next generation sequencing has a limited ability to identify structural variations. By combining comprehensive analysis of structural variants (SVs), single-nucleotide variants (SNVs), and small insertions-deletions, new subtype-defining and therapeutic targets may be detected. We analyzed the landscape of somatic alterations in 60 pediatric patients diagnosed with the most common BCP-ALL subtypes, ETV6::RUNX1 + and classical hyperdiploid (HD), using conventional cytogenetics, single nucleotide polymorphism (SNP) array, whole exome sequencing (WES), and the novel optical genome mapping (OGM) technique. Ninety-five percent of SVs detected by cytogenetics and SNP-array were verified by OGM. OGM detected an additional 677 SVs not identified using the conventional methods, including (subclonal) IKZF1 deletions. Based on OGM, ETV6::RUNX1 + BCP-ALL harbored 2.7 times more SVs than HD BCP-ALL, mainly focal deletions. Besides SVs in known leukemia development genes ( ETV6 , PAX5 , BTG1, CDKN2A ), we identified 19 novel recurrently altered regions (in n ≥ 3) including 9p21.3 ( FOCAD/HACD4 ), 8p11.21 ( IKBKB ), 1p34.3 ( ZMYM1 ), 4q24 ( MANBA ), 8p23.1 ( MSRA ), and 10p14 ( SFMBT2 ), as well as ETV6::RUNX1+ subtype-specific SVs (12p13.1 ( GPRC5A ), 12q24.21 ( MED13L ), 18q11.2 ( MIB1 ), 20q11.22 ( NCOA6 )). We detected 3 novel fusion genes ( SFMBT2::DGKD, PDS5B::STAG2, and TDRD5::LPCAT2 ), for which the sequence and expression were validated by long-read and whole transcriptome sequencing, respectively. OGM and WES identified double hits of SVs and SNVs ( ETV6 , BTG1 , STAG2 , MANBA , TBL1XR1 , NSD2 ) in the same patient demonstrating the power of the combined approach to define the landscape of genomic alterations in BCP-ALL.
Sentinel Node Performance by Laparotomy in A Large Myomatous Uterus With Early-Stage Endometrial Cancer: Lessons to be Learned
Authors: Stamatios Petousis, Aristarchos Almperis, Chrysoula Margioula-Siarkou, Eleni Nixarlidou, Konstantinos Dinas, Stamatios Petousis
Journal: International Journal of Surgery (2023)
Large Cystic Lymphangioma of The Pancreas: Unusual Finding with Differential Diagnosis and Therapeutic Considerations
Authors: Nikolaos Tasis, Arnaouti M, Fradelos E, Korkolis DP, Manatakis DK, Mpalampou E, Nikolaos Tasis, Sarafi A, Skafida E, Tsouknidas I
Journal: International Journal of Surgery (2023)
Spatially resolved, high-dimensional transcriptomics sorts out the evolution of biphasic malignant pleural mesothelioma: new paradigms for immunotherapy
Authors: F Torricelli, B Donati, F Reggiani, V Manicardi, S Piana, R Valli, F Lococo, Alessia Ciarrocchi
Journal: Molecular Cancer (2023)

Abstract Background Malignant Pleural Mesothelioma (MPM) is a dreadful disease escaping the classical genetic model of cancer evolution and characterized by wide heterogeneity and transcriptional plasticity. Clinical evolution of MPM is marked by a progressive transdifferentiation that converts well differentiated epithelioid (E) cells into undifferentiated and pleomorphic sarcomatoid (S) phenotypes. Catching the way this transition takes place is necessary to understand how MPM develops and progresses and it is mandatory to improve patients’ management and life expectancy. Bulk transcriptomic approaches, while providing a significant overview, failed to resolve the timing of this evolution and to identify the hierarchy of molecular events through which this transition takes place. Methods We applied a spatially resolved, high-dimensional transcriptomic approach to study MPM morphological evolution. 139 regions across 8 biphasic MPMs (B-MPMs) were profiled using the GeoMx™Digital Spatial Profiler to reconstruct the positional context of transcriptional activities and the spatial topology of MPM cells interactions. Validation was conducted on an independent large cohort of 84 MPMs by targeted digital barcoding analysis. Results Our results demonstrated the existence of a complex circular ecosystem in which, within a strong asbestos-driven inflammatory environment, MPM and immune cells affect each other to support S-transdifferentiation. We also showed that TGFB1 polarized M2-Tumor Associated Macrophages foster immune evasion and that TGFB1 expression correlates with reduced survival probability. Conclusions Besides providing crucial insights into the multidimensional interactions governing MPM clinical evolution, these results open new perspectives to improve the use of immunotherapy in this disease.
Targeting miRNA by CRISPR/Cas in cancer: advantages and challenges
Authors: Bashdar Mahmud Hussen, Mohammed Fatih Rasul, Snur Rasool Abdullah, Hazha Jamal Hidayat, Goran Sedeeq Hama Faraj, Fattma Abodi Ali, Abbas Salihi, Aria Baniahmad, Soudeh Ghafouri-Fard, Milladur Rahman, Mark C. Glassy, Wojciech Branicki, Mohammad Taheri
Journal: Military Medical Research (2023)

Clustered regulatory interspaced short palindromic repeats (CRISPR) has changed biomedical research and provided entirely new models to analyze every aspect of biomedical sciences during the last decade. In the study of cancer, the CRISPR/CRISPR-associated protein (Cas) system opens new avenues into issues that were once unknown in our knowledge of the noncoding genome, tumor heterogeneity, and precision medicines. CRISPR/Cas-based gene-editing technology now allows for the precise and permanent targeting of mutations and provides an opportunity to target small non-coding RNAs such as microRNAs (miRNAs). However, the development of effective and safe cancer gene editing therapy is highly dependent on proper design to be innocuous to normal cells and prevent introducing other abnormalities. This study aims to highlight the cutting-edge approaches in cancer-gene editing therapy based on the CRISPR/Cas technology to target miRNAs in cancer therapy. Furthermore, we highlight the potential challenges in CRISPR/Cas-mediated miRNA gene editing and offer advanced strategies to overcome them.
Exosome-mediated miR-144-3p promotes ferroptosis to inhibit osteosarcoma proliferation, migration, and invasion through regulating ZEB1
Authors: Mingyang Jiang, Yiji Jike, Kaicheng Liu, Fu Gan, Ke Zhang, Mingjing Xie, Junlei Zhang, Chuanliang Chen, Xiaochong Zou, Xiaohong Jiang, Yongheng Dai, Weikui Chen, Yue Qiu, Zhandong Bo
Journal: Molecular Cancer (2023)

Abstract Background Osteosarcoma (OS) is the most prevalent orthopedic malignancy with a dismal prognosis. The high iron absorption rate in OS cells of patients suggests that ferroptosis may be related to the progression of OS, but its potential molecular regulatory role is still unclear. Based on the ability to couple with exosomes for targeted delivery of signals, exosome-derived micro ribonucleic acids (miRNAs) can potentially serve as diagnostic biomarkers for OS. Methods We identified ferroptosis-related miRNAs and messenger ribonucleic acids(mRNAs) in OS using bioinformatics analysis and performed survival analysis. Then we measured miRNA expression levels through exosome microarray sequencing, and used RT-qPCR and IHC to verify the expression level of miR-144-3p and ZEB1. Stable gene expression cell lines were fabricated for in vitro experiments. Cell viability, migration and invasion were determined by CCK-8 and transwell experiment. Use the corresponding reagent kit to detect GSH/GSSG ratio, Fe 2+ level, MDA level and ROS level, and measure the expression levels of GPX4, ACSL4 and xCT through RT-qPCR and WB. We also constructed nude mice model for in vivo experiments. Finally, the stability of the miRNA/mRNA axis was verified through functional rescue experiments. Results Low expression of miR-144-3p and high expression of ZEB1 in OS cell lines and tissues was observed. Overexpression of miR-144-3p can promote ferroptosis, reduce the survival ability of OS cells, and prevent the progression of OS. In addition, overexpression of miR-144-3p can downregulate the expression of ZEB1 in cell lines and nude mice. Knockdown of miR-144-3p has the opposite effect. The functional rescue experiment validated that miR-144-3p can regulate downstream ZEB1, and participates in the occurrence and development of OS by interfering with redox homeostasis and iron metabolism. Conclusions MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of OS cells. Graphical Abstract
Sensitive inference of alignment-safe intervals from biodiverse protein sequence clusters using EMERALD
Authors: Andreas Grigorjew, Artur Gynter, Fernando H. C. Dias, Benjamin Buchfink, Hajk-Georg Drost, Alexandru I. Tomescu
Journal: Genome biology (2023)

Sequence alignments are the foundations of life science research, but most innovation so far focuses on optimal alignments, while information derived from suboptimal solutions is ignored. We argue that one optimal alignment per pairwise sequence comparison is a reasonable approximation when dealing with very similar sequences but is insufficient when exploring the biodiversity of the protein universe at tree-of-life scale. To overcome this limitation, we introduce pairwise alignment-safety to uncover the amino acid positions robustly shared across all suboptimal solutions. We implement EMERALD, a software library for alignment-safety inference, and apply it to 400k sequences from the SwissProt database.
Context-dependent T-cell Receptor Gene Repertoire Profiles in Proliferations of T Large Granular Lymphocytes
Authors: Jorn L.J.C. Assmann, Elisavet Vlachonikola, Pieter M. Kolijn, Andreas Agathangelidis, Nikolaos Pechlivanis, Apostolia Papalexandri, Kostas Stamatopoulos, Anastasia Chatzidimitriou, Anton W. Langerak
Journal: HemaSphere (2023)

T cell large granular lymphocyte (T-LGL) lymphoproliferations constitute a disease spectrum ranging from poly/oligo to monoclonal. Boundaries within this spectrum of proliferations are not well established. T-LGL lymphoproliferations co-occur with a wide variety of other diseases ranging from autoimmune disorders, solid tumors, hematological malignancies, post solid organ, and hematopoietic stem cell transplantation, and can therefore arise as a consequence of a wide variety of antigenic triggers. Persistence of a dominant malignant T-LGL clone is established through continuous STAT3 activation. Using next-generation sequencing, we profiled a cohort of 27 well-established patients with T-LGL lymphoproliferations, aiming to identify the subclonal architecture of the T-cell receptor beta (TRB) chain gene repertoire. Moreover, we searched for associations between TRB gene repertoire patterns and clinical manifestations, with the ultimate objective of discriminating between T-LGL lymphoproliferations developing in different clinical contexts and/or displaying distinct clinical presentation. Altogether, our data demonstrates that the TRB gene repertoire of patients with T-LGL lymphoproliferations is context-dependent, displaying distinct clonal architectures in different settings. Our results also highlight that there are monoclonal T-LGL cells with or without STAT3 mutations that cause symptoms such as neutropenia on one end of a spectrum and reactive oligoclonal T-LGL lymphoproliferations on the other. Longitudinal analysis revealed temporal clonal dynamics and showed that T-LGL cells might arise as an epiphenomenon when co-occurring with other malignancies, possibly reactive toward tumor antigens.